1. Field of the Invention
The present invention relates generally to the fields of organic chemical synthesis and medicinal organic plant compounds. More specifically, the present invention relates to methods for the large-scale synthesis of naturally occurring medicinal organic compounds.
2. Description of the Related Art
Malaria is the leading cause of child mortality worldwide. However, the mosquito-borne disease has been classified as an “orphan disease” because the poverty of the afflicted regions does not sustain for-profit drug discovery. The rapid evolution of drug-resistant strains of the disease magnifies the tragedy by rendering cheaper treatments ineffective. Other than mosquito eradication strategies, historically the most effective approaches to curbing malaria have been small molecule-based treatments derived from natural products, for example, plants.
Avery et al. investigated the activity of Flindersia alkaloids (1-3) which demonstrate toxicity against Plasmodium falciparum, the malarial strain responsible for most deaths. Several of the compounds, for example, flinderoles A, B and C, isoborreverine, dimethylisoborreverine, chloroquine and artemisinin show effectiveness toward chloroquine-resistant falciparum strains at concentrations that do not affect mammalian cells' viability. The Avery group determined that while the Flindersia alkaloids target the hemoglobin metabolism of P. falciparum, they do not mimic the heme-binding action of the quinoline alkaloids. It is possible that they could act nonspecifically either by inhibiting a known protein for hemoglobin metabolism, e.g., a hemoglobin protease or a histidine-rich protein that sequesters toxic heme as hemozoin, or by inhibiting an as-yet-undisclosed target, however, the mechanism of these compounds remains unknown. Consequently, further research on the development of new antimalarial therapeutics is needed.
There is a recognized need for improved methods of biomimetic synthesis of naturally occurring organic compounds to gain access to these compounds for biological testing and development of therapeutic compounds based on the same. The prior art is deficient in the lack of a large-scale biomimetic synthesis of organic plant compounds via a method requiring few steps. The present invention fulfills this longstanding need and desire in the art.